Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

TY - JOUR

T1 - Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

AU - Engelholm, S A

AU - Spang-Thomsen, M

AU - Vindeløv, L L

AU - Brünner, N A

N1 - Keywords: Animals; Carcinoma, Small Cell; Cell Cycle; DNA; Dose-Response Relationship, Drug; Drug Resistance; Flow Cytometry; Humans; Interphase; Lung Neoplasms; Melphalan; Mice; Mice, Nude; Neoplasm Transplantation

PY - 1986

Y1 - 1986

N2 - A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow cytometric DNA analysis. Melphalan produced a dose-related S phase accumulation in the two sensitive tumors, whereas no changes in the cell cycle distribution were found in the resistant tumor. The size of S phase accumulation correlated to the chemosensitivity in vivo. For low concentrations of melphalan, the S phase accumulation was accompanied by G2 + M accumulation. The results indicate that the method may be extended to sensitivity testing of human solid tumors, including screening for new agents.

AB - A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow cytometric DNA analysis. Melphalan produced a dose-related S phase accumulation in the two sensitive tumors, whereas no changes in the cell cycle distribution were found in the resistant tumor. The size of S phase accumulation correlated to the chemosensitivity in vivo. For low concentrations of melphalan, the S phase accumulation was accompanied by G2 + M accumulation. The results indicate that the method may be extended to sensitivity testing of human solid tumors, including screening for new agents.

U2 - 10.1002/cyto.990070304

DO - 10.1002/cyto.990070304

M3 - Journal article

C2 - 3011370

SN - 0916-6920

VL - 7

SP - 243

EP - 250

JO - Cytometry Research

JF - Cytometry Research

IS - 3

ER -